Loss of stromal VEGFR2 protects against ischemic acute kidney injury by preserving the renal microvasculature
- 1University of Pittsburgh
Abstract
Injury to the renal microvasculature, particularly the peritubular capillaries, is a defining feature of ischemic acute kidney injury (AKI). Vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a central regulator of endothelial cell survival, proliferation, migration, and vascular remodeling. Although VEGFR2 has been extensively studied in endothelial cells, accumulating evidence suggests that it is also expressed in non-endothelial cell populations, where it may regulate tissue-specific responses to injury. Here, using publicly available single-cell or single-nucleus RNA sequencing data from human and mouse kidneys, we identified VEGFR2 expression in renal stromal populations. Immunostaining further detected phosphorylated VEGFR2 in the renal stroma of mouse kidneys. To determine the functional role of stromal VEGFR2, we utilized renal stroma-specific Vegfr2 KO mice. Stromal VegfR2 deletion attenuated kidney injury after renal ischemia/reperfusion injury (IRI), as evidenced by reduced tubular injury, preservation of renal blood flow, decreased endothelial oxidative stress, and maintenance of the renal microvasculature. Stromal Vegfr2-deficient kidneys also exhibited increased Angpt1 and Tek levels, enhanced endothelial ERK activation, and preserved endothelial adherent junctions. Taken together, these findings reveal an unexpected role for VEGFR2 in the renal stromal lineage and highlight stromal-endothelial communication as a potential therapeutic target for preserving microvascular integrity after ischemic AKI.
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BibTeX
@misc{chiba2026loss,
title = {{Loss of stromal VEGFR2 protects against ischemic acute kidney injury by preserving the renal microvasculature}},
author = {T. Chiba and A. Oda and A. Kinoshita and K. Kamijo and A. Bhasin and D. M. Cerqueira and E. Mukherjee and K. E. Pfister and Y. Hidaka and Y. Sakurahara and K. V. Maringer and N. M. Rogers and J. Ho and S. Sims-Lucas},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762337},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762337v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Loss of stromal VEGFR2 protects against ischemic acute kidney injury by preserving the renal microvasculature
AU - T. Chiba
AU - A. Oda
AU - A. Kinoshita
AU - K. Kamijo
AU - A. Bhasin
AU - D. M. Cerqueira
AU - E. Mukherjee
AU - K. E. Pfister
AU - Y. Hidaka
AU - Y. Sakurahara
AU - K. V. Maringer
AU - N. M. Rogers
AU - J. Ho
AU - S. Sims-Lucas
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762337
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762337v1
AB - Injury to the renal microvasculature, particularly the peritubular capillaries, is a defining feature of ischemic acute kidney injury (AKI). Vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a central regulator of endothelial cell survival, proliferation, migration, and vascular remodeling. Although VEGFR2 has been extensively studied in endothelial cells, accumulating evidence suggests that it is also expressed in non-endothelial cell populations, where it may regulate tissue-specific responses to injury. Here, using publicly available single-cell or single-nucleus RNA sequencing data from human and mouse kidneys, we identified VEGFR2 expression in renal stromal populations. Immunostaining further detected phosphorylated VEGFR2 in the renal stroma of mouse kidneys. To determine the functional role of stromal VEGFR2, we utilized renal stroma-specific Vegfr2 KO mice. Stromal VegfR2 deletion attenuated kidney injury after renal ischemia/reperfusion injury (IRI), as evidenced by reduced tubular injury, preservation of renal blood flow, decreased endothelial oxidative stress, and maintenance of the renal microvasculature. Stromal Vegfr2-deficient kidneys also exhibited increased Angpt1 and Tek levels, enhanced endothelial ERK activation, and preserved endothelial adherent junctions. Taken together, these findings reveal an unexpected role for VEGFR2 in the renal stromal lineage and highlight stromal-endothelial communication as a potential therapeutic target for preserving microvascular integrity after ischemic AKI.
ER -